Slow waves represent one of the prominent EEG signatures of non-rapid eye movement (non-REM) sleep and are thought to play an important role in the cellular and network plasticity that occurs during this behavioral state. These slow waves of natural sleep are currently considered to be exclusively generated by intrinsic and synaptic mechanisms within neocortical territories, although a role for the thalamus in this key physiological rhythm has been suggested but never demonstrated. Combining neuronal ensemble recordings, microdialysis, and optogenetics, here we show that the block of the thalamic output to the neocortex markedly (up to 50%) decreases the frequency of slow waves recorded during non-REM sleep in freely moving, naturally sleeping-waking rats. A smaller volume of thalamic inactivation than during sleep is required for observing similar effects on EEG slow waves recorded during anesthesia, a condition in which both bursts and single action potentials of thalamocortical neurons are almost exclusively dependent on T-type calcium channels. Thalamic inactivation more strongly reduces spindles than slow waves during both anesthesia and natural sleep. Moreover, selective excitation of thalamocortical neurons strongly entrains EEG slow waves in a narrow frequency band (0.75-1.5 Hz) only when thalamic T-type calcium channels are functionally active. These results demonstrate that the thalamus finely tunes the frequency of slow waves during non-REM sleep and anesthesia, and thus provide the first conclusive evidence that a dynamic interplay of the neocortical and thalamic oscillators of slow waves is required for the full expression of this key physiological EEG rhythm.

SummaryGrowing evidence suggests that distributed spatial attention may invoke theta (3–9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is, however, not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields (RFs) elicits rhythmic multi-unit activity (MUA) at 3–6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RTs) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at theta frequencies. These findings show that theta rhythmic neuronal activity can arise from competitive RF interactions and that this rhythm may result in rhythmic RTs potentially subserving attentional sampling.

To resolve this apparent discrepancy, we longitudinally assessed neuronal functions of macaque area V4 using chronically implanted electrode arrays before and after creating a permanent aspiration lesion in V1. During the month after lesioning, we observed weak yet significant spiking activity in response to stimuli presented to the lesion-affected part of the visual field. These V1-independent responses showed sensitivity for motion and likely reflect the effect of V1-bypassing geniculate input into extrastriate areas.

The local field potential (LFP) in visual cortex is typically characterized by the following spectral pattern: before the onset of a visual stimulus, low-frequencyoscillations(beta,12-20Hz)dominate,whereasduringthepresentationofastimulustheseoscillationsdiminishandarereplaced by fluctuations at higher frequencies (gamma, Ͼ30 Hz). The origin of beta oscillations in vivo remains unclear, as is the basis of their suppression during visual stimulation. Here we investigate the contribution of ascending input from primary visual cortex (V1) to beta oscillation dynamics in extrastriate visual area V4 of behaving monkeys. We recorded LFP activity in V4 before and after resecting a portion of V1. After the surgery, the visually induced gamma LFP activity in the lesion projection zone of V4 was markedly reduced, consistent with previously reported spiking responses (Schmid et al., 2013). In the beta LFP range, the lesion had minimal effect on the normal pattern of spontaneous oscillations. However, the lesion led to a surprising and permanent reversal of the normal beta suppression during visual stimulation, with visual stimuli eliciting beta magnitude increases up to 50%, particularly in response to moving stimuli. This reversed beta activity pattern was specific to stimulus locations affected by the V1 lesion. Our results shed light on the mechanisms of beta activity in extrastriate visual cortex: The preserved spontaneous oscillations point to a generation mechanism independent of the geniculostriate pathway, whereas the positive beta responses support the contribution of visual information to V4 via direct thalamo-extrastriate projections.

HighlightsOptogenetics and microdialysis can be successfully combined.How to manipulate circuits of spontaneous and evoked activities with drugs and lights?Thalamic control of delta waves and sleep spindles.